AR092474A1 - Moduladores heterociclicos de los receptores de hormonas nucleares - Google Patents

Moduladores heterociclicos de los receptores de hormonas nucleares

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AR092474A1
AR092474A1 ARP130103182A ARP130103182A AR092474A1 AR 092474 A1 AR092474 A1 AR 092474A1 AR P130103182 A ARP130103182 A AR P130103182A AR P130103182 A ARP130103182 A AR P130103182A AR 092474 A1 AR092474 A1 AR 092474A1
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Argentina
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optionally substituted
alkyl
heteroaryl
ring
cycloalkyl
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ARP130103182A
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Burchat Andrew
M Friedman Michael
D Gordon Thomas
C Ihle David
Y Lo Schiavo Gloria
D Mullen Kelly
Wang Lei
P Cusack Kevin
J Morytko Michael
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Abbvie Inc
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Publication of AR092474A1 publication Critical patent/AR092474A1/es

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    • C07D417/08—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing alicyclic rings
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    • C07D491/10—Spiro-condensed systems
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    • C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
    • C07D491/20—Spiro-condensed systems

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Abstract

Los compuestos de fórmula (1) son útiles en el tratamiento de afecciones relacionadas con la inflamación. Los compuestos de la presente son de utilidad para el tratamiento de condiciones inmunológicas y oncológicas. Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1), o una sal farmacéuticamente aceptable, prodroga, metabolito biológicamente activo, isómero, o estereoisómero del mismo, donde: el Anillo A es un anillo heteroarilo o un anillo heterocíclico insaturado o parcialmente insaturado, donde: G es S, O, CR¹, C(R¹)₂, N, o NR¹; J es C, CR¹, C(R¹)₂, O, N, o NR¹; y, L es C, CR¹, C(R¹)₂, N, o NR¹; siempre que J no es O cuando G es O ó S; y, el Anillo A es una pirazina opcionalmente sustituida, piridina opcionalmente sustituida, o fenilo opcionalmente sustituido; el Anillo B es un anillo de siete miembros opcionalmente sustituido con deuterio, donde: X es -C(R⁵)₂-, -C(R⁵)=, -C(=O)-, N(Rᵃ), -S-, -S(O)-, o -S(O)₂-; o cuando X es -C(R⁵)₂-, ambos sustituyentes R⁵, junto con el átomo de carbono al cual se encuentran unidos, opcionalmente forman un anillo ciclopropilo espiro al Anillo B; Y es -C(R⁵)₂C(R⁵)₂-, =C(R⁵)C(R⁵)₂-, -C(R⁵)₂C(R⁵)=, =C(R⁵)C(R⁵)=, -N(Rᵃ)C(R⁵)₂-, -C(R⁵)₂N(Rᵃ)-, -C(=O)C(R⁵)₂-, -C(R⁵)₂C(=O)-, -O-C(=O)-, -C(=O)-O-, -OC(R⁵)₂-, o -C(R⁵)₂-O-; siempre que X-Y no forme enlaces -N(Rᵃ)-C(R⁵)₂-N(Rᵃ)-, S-C(R⁵)₂-N(Rᵃ)-, -S-C(R⁵)₂-O-, -O-C(R⁵)₂-N(Rᵃ)-, -C(=O)C(=O)-C(R⁵)₂-, -C(=O)-C(=O)-O-, -N(Rᵃ)-C(R⁵)₂-O-, -O-C(R⁵)₂-O-, -S-C(=O)C(R⁵)₂-, -S-C(=O)-O-, o -S-C(R⁵)₂-O-; y siempre que X-Y no resulte en un átomo de oxígeno adyacente a un átomo de nitrógeno, un átomo de azufre u otro átomo de oxígeno; y siempre que X-Y no resulte en dos átomos de hidrógeno adyacentes entre sí; el Anillo C es un anillo carbociclilo o heterociclilo saturado o parcialmente insaturado de cinco o seis miembros opcionalmente sustituido; R¹ es en forma independiente H, deuterio, -Br, -Cl, -F, -CF₃, -CN, -ORᵇ, alquilen C₁₋₃-Rᵇ opcionalmente sustituido, alquilo C₁₋₃ opcionalmente sustituido, arilo opcionalmente sustituido, cicloalquilo C₃₋₆ opcionalmente sustituido, heteroarilo opcionalmente sustituido, heterociclo opcionalmente sustituido, -S(O)₂Rᵇ-, =O, o N(Rᵃ)(Rᵇ); R¹ᵃ es en forma independiente H, deuterio, -Br, -Cl, -F, -CF₃, -CN, alquilo C₁₋₆ opcionalmente sustituido, cicloalquilo C₃₋₆ opcionalmente sustituido, heterociclo opcionalmente sustituido, S(O)₂-Rᵃ, o -N(Rᵃ)₂; R² es -CD₃, -CH₂CD₃, -CN, -alilo, -CH₂NHC(=O)alquilo C₁₋₃, -CH₂NHSO₂-alquilo C₁₋₃, -N(R)-SO₂-alquilo opcionalmente sustituido; -N(R)(Rᵍ), -N(R)-cicloalquilo opcionalmente sustituido, -N(R)-arilo opcionalmente sustituido, -N(R)-heteroarilo opcionalmente sustituido, -N(R)heterociclo opcionalmente sustituido, -N(R)C(O)-alquilo opcionalmente sustituido, -N(R)₂, C(O)N(Rᵃ)₂, -CH₂-arilo opcionalmente sustituido, -CH₂-cicloalquilo C₃₋₆ opcionalmente sustituido, alquilo C₁₋₃ opcionalmente sustituido, alquenilo C₂₋₃ opcionalmente sustituido, -CH₂-heteroarilo opcionalmente sustituido, -(CH₂)ₙ₁-heterociclo opcionalmente sustituido, -C(Rᵈ)₂-Rᵉ, o -C(=O)Rᵉ, siempre que cuando R² es -C(Rᵈ)₂-Rᵉ, sólo un Rᵈ puede ser OH; R³ es en forma independiente una unión, deuterio, -CD₃, -CF₃, -N(Rᵃ)SO₂Rᶜ, -N(Rᵃ)CORᶜ, -CON(Rᵃ)Rᶜ, -N(Rᵃ)COORᶜ, -N(Rᵃ)₂, -O-C(O)NR-alquilo opcionalmente sustituido, alquinilo C₂₋₆ opcionalmente sustituido, =O, -ORᵃ, -ORᶠ, alquilo C₁₋₄ opcionalmente sustituido, alquil C₁₋₄-O-alquilo C₁₋₄ opcionalmente sustituido, -(C(Rᵃ)²)ʳ-cicloalquilo C₃₋₆ sustituido, -(C(Rᵃ)₂)ʳ-arilo opcionalmente sustituido, -(C(Rᵃ)₂)ʳ-heteroarilo opcionalmente sustituido, -(C(Rᵃ)₂)ʳ-N(Rᵃ)-heteroarilo opcionalmente sustituido, -(C(Rᵃ)₂)ʳ-N(Rᵃ)-(C(Rᵃ)₂)ʳ-arilo opcionalmente sustituido, o una unidad espirocíclica carbocíclica o heterocíclica unida al anillo C; R⁴ es una unión, H, deuterio, -CD₃, -F, alquilo C₁₋₃ opcionalmente sustituido, -OH o -O-alquilo C₁₋₃ opcionalmente sustituido; R⁵ es en forma independiente H, deuterio, -CD₃, -F, -CF₃, -N(Rᵃ), -ORᵃ, o alquilo C₁₋₃ opcionalmente sustituido; y, Rᵃ es en forma independiente H, deuterio, cicloalquilo C₃₋₆ opcionalmente sustituido, o alquilo C₁₋₃ opcionalmente sustituido; Rᵇ es H, alquilo C₁₋₃ opcionalmente sustituido, arilo opcionalmente sustituido, cicloalquilo C₃₋₆ opcionalmente sustituido, heteroarilo opcionalmente sustituido, o heterociclo opcionalmente sustituido; Rᶜ es alquilo C₁₋₃ opcionalmente sustituido o arilo opcionalmente sustituido; Rᵈ es en forma independiente H, deuterio, -OH, o alquilo C₁₋₆ opcionalmente sustituido; Rᵉ es -CF₃, arilo opcionalmente sustituido, alquilo C₁₋₆ opcionalmente sustituido, cicloalquilo C₃₋₆ opcionalmente sustituido, heteroarilo opcionalmente sustituido, o heterociclo opcionalmente sustituido; Rᶠ es -H, -SO₂NH₂, -CH₂CO₂H, -CH₂CONH₂, -P(=O)(OH)(OH), -C(O)-alquilo C₁₋₆ opcionalmente sustituido, -C(O)N(alquilo C₁₋₆ opcionalmente sustituido)₂, -C(O)(alquilo C₁₋₆ opcionalmente sustituido)₂, -C(O)-arilo opcionalmente sustituido, -C(O)-heterociclo opcionalmente sustituido, -C(O)cicloalquilo C₃₋₆ opcionalmente sustituido, -C(O)-CR₂-heterociclo opcionalmente sustituido o -C(O)-CR₂-heteroarilo opcionalmente sustituido; Rᵍ es -CH₂-cicloalquilo C₃₋₆ opcionalmente sustituido, -CH₂-heteroarilo opcionalmente sustituido, o -CH₂-heterociclo opcionalmente sustituido; R es en forma independiente H o alquilo C₁₋₃; m es 0, 1 ó 2; n1 es en forma independiente 0 ó 1; p es 1, 2, 3 ó 4; y r es en forma independiente 0, 1 ó 2.
ARP130103182A 2012-09-07 2013-09-06 Moduladores heterociclicos de los receptores de hormonas nucleares AR092474A1 (es)

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